Guest blogger, Dr. Curtis L. Triplitt, is a Clinical Associate Professor of Medicine at the University of Texas Health Science Center at San Antonio (UTHSCSA) and works at the Texas Diabetes Institute, San Antonio, TX as a researcher, clinician, and educator.
t the 52nd Annual EASD meeting there were several exciting studies discussed.
The Gut and Disease
There were several interesting microbiome presentations. The most interesting one was the TEDDY trial from Baylor in Texas. Microbiome samples were analyzed from many children at risk of type 1 DM. Islet autoimmunity was explored by the researchers and an association was found with low bacterial diversity and microbiome instability. What that means is, as the child grew, the microbiome changed drastically compared to the microbiomes of the children in the control group. The presenter mentioned his interpretation of this finding is that islet autoimmunity is increased in children who fail to reach and maintain microbiome maturity. Future studies will see if supporting the microbiome may decrease autoimmunity conversion.
In a second presentation, the FinnDiane trial, it was found that intestinal markers of inflammation were elevated prior to type 1 DM patients developing nephropathy. This was explained through a complex series of events, but overall it appears that short-chain fatty acid intake, or production by the microbiome, may be associated with long-term complications seen in type 1 DM. The gut continues to give us clues that it is involved in “systemic” diseases…and may signal we truly are what we eat.
The biggest buzz of the meeting was around the study called SUSTAIN-6, which used a weekly injectable GLP-1 receptor agonist, not available, named semaglutide. The A1C was reduced 1.1 percent and 1.5percent with the lower and higher dose of semaglutide and weight was reduced by 4kg over about 2 years. Semaglutide reduced the risk of death, an MI, or stroke by a significant 26 percent and it reduced the risk of worsening of nephropathy by 36 percent. Negatively, the risk of retinopathy increased. The speakers mentioned that worsening eye disease can happen with rapid glycemic improvement in type 1 DM, but whether this is the cause is unknown. Safety worries were similar to other GLP-1 RA’s with nausea/vomiting causing most of the side effects. There was not an increased risk of pancreatitis, cancer, or other serious problems. Recall that at this year’s ADA, a study with liraglutide (Victoza), LEADER, reported positive reductions in death in type 2 DM patients with CV disease. Interestingly, semaglutide is very similar in structure to liraglutide (both are made by Novo), and so comparisons are inevitable. Liraglutide, but not semaglutide, reported a reduction in the risk of death, so we can feel comfortable continuing to recommend liraglutide.
If you want to read further, both reports were published in the New England Journal of Medicine. Our patients are starting to hear about cardiovascular trials completed in diabetes, and I have personally been asked by several if they should take one of these medications. These trials only enrolled/showed benefit in patients with documented CV disease and so for now, not all type 2 DM patients should be switched to these therapies.
Providers have started to use GLP-1RA’s in combination with SGLT-2 inhibitors. Both help with weight, blood pressure, and have a low risk of hypoglycemia. Surprisingly, there have been very few studies on this combination. The DURATION-8 trial looked at the combination of exenatide-ER (Bydureon) with dapagliflozin (Farxiga) in type 2 DM. Patients who were taking metformin and continued to have an uncontrolled A1C (9.3%) added either Farxiga, Bydureon, or both to their antihyperglycemic regimen for about six months. The A1C was reduced 2.0 percent in the combination group, 1.6 percent in the Bydureon group, and 1.4 percent in the Farxiga group. Though the A1C reduction was not additive between the two drugs, weight loss (-3.4kg) and the systolic blood pressure (-4.2mmHg) reduction was additive. Side effects were as expected for both drugs with no surprises, and a low risk of hypoglycemia. This combination appears to really help some patients lose weight and lower their blood pressure on top of helping their glycemic control. I would expect we shall see more of it used in the future.